The N-methyl-d-aspartate receptor antagonist CPP alters synapse and spine structure and impairs long-term potentiation and long-term depression induced morphological plasticity in dentate gyrus of the awake rat

Long-term morphological synaptic changes associated with homosynaptic long-term potentiation (LTP) and heterosynaptic long-term depression (LTD) in vivo, in awake adult rats were analyzed using three-dimensional (3-D) reconstructions of electron microscope images of ultrathin serial sections from the molecular layer of the dentate gyrus. For the first time in morphological studies, the specificity of the effects of LTP and LTD on both spine and synapse ultrastructure was determined using an N-methyl-d-aspartate (NMDA) receptor antagonist CPP (3-[(R)-2-carboxypiperazin-4-yl]-propyl-1-phosphonic acid). There were no differences in synaptic density 24 h after LTP or LTD induction, and CPP alone had no effect on synaptic density. LTP increased significantly the proportion of mushroom spines, whereas LTD increased the proportion of thin spines, and both LTP and LTD decreased stubby spine number. Both LTP and LTD increased significantly spine head evaginations (spinules) into synaptic boutons and CPP blocked these changes. Synaptic boutons were smaller after LTD, indicating a pre-synaptic effect. Interestingly, CPP alone decreased bouton and mushroom spine volumes, as well as post-synaptic density (PSD) volume of mushroom spines.These data show similarities, but also some clear differences, between the effects of LTP and LTD on spine and synaptic morphology. Although CPP blocks both LTP and LTD, and impairs most morphological changes in spines and synapses, CPP alone was shown to exert effects on aspects of spine and synaptic structure

Heme oxygenase-1 derived carbon monoxide suppresses Aβ1-42 toxicity in astrocytes

Neurodegeneration in Alzheimer’s disease (AD) is extensively studied, and the involvement of astrocytes and other cell types in this process has been described. However, the responses of astrocytes themselves to amyloid peptides ((A; the widely accepted major toxic factor in AD) is less well understood. Here, we show that A(1-42) is toxic to primary cultures of astrocytes. Toxicity does not involve disruption of astrocyte Ca2+ homeostasis, but instead occurs via formation of the toxic reactive species, peroxynitrite. Thus, A(1-42) raises peroxynitrite levels in astrocytes, and A(1-42) toxicity can be inhibited by antioxidants, or by inhibition of nitric oxide (NO) formation (reactive oxygen species (ROS) and NO combine to form peroxynitrite), or by a scavenger of peroxynitrite. Increased ROS levels observed following A(1-42) application were derived from NADPH oxidase. Induction of heme oxygenase-1 (HO-1) protected astrocytes from A(1-42) toxicity, and this protective effect was mimicked by application of the carbon monoxide (CO) releasing molecule CORM-2, suggesting HO-1 protection was attributable to its formation of CO. CO suppressed the rise of NADPH oxidase-derived ROS caused by A(1-42). Under hypoxic conditions (0.5% O2, 48h) HO-1 was induced in astrocytes and A(1-42) toxicity was significantly reduced, an effect which was reversed by the specific HO-1 inhibitor, QC-15. Our data suggest that A(1-42) is toxic to astrocytes, but that induction of HO-1 affords protection against this toxicity due to formation of CO. HO-1 induction, or CO donors, would appear to present attractive possible approaches to provide protection of both neuronal and non-neuronal cell types from the degenerative effects of AD in the central nervous system

Rethinking Research Ethics for Latinos: The Policy Paradox of Health Reform and the Role of Social Justice

http://dx.doi.org/10.1080/10508422.2012.72999

Heme oxygenase-1 derived carbon monoxide suppresses Aβ1-42 toxicity in astrocytes

Neurodegeneration in Alzheimer’s disease (AD) is extensively studied, and the involvement of astrocytes and other cell types in this process has been described. However, the responses of astrocytes themselves to amyloid β peptides ((Aβ; the widely accepted major toxic factor in AD) is less well understood. Here, we show that Aβ(1-42) is toxic to primary cultures of astrocytes. Toxicity does not involve disruption of astrocyte Ca2+ homeostasis, but instead occurs via formation of the toxic reactive species, peroxynitrite. Thus, Aβ(1-42) raises peroxynitrite levels in astrocytes, and Aβ(1-42) toxicity can be inhibited by antioxidants, or by inhibition of nitric oxide (NO) formation (reactive oxygen species (ROS) and NO combine to form peroxynitrite), or by a scavenger of peroxynitrite. Increased ROS levels observed following Aβ(1-42) application were derived from NADPH oxidase. Induction of heme oxygenase-1 (HO-1) protected astrocytes from Aβ(1-42) toxicity, and this protective effect was mimicked by application of the carbon monoxide (CO) releasing molecule CORM-2, suggesting HO-1 protection was attributable to its formation of CO. CO suppressed the rise of NADPH oxidase-derived ROS caused by Aβ(1-42). Under hypoxic conditions (0.5% O2, 48h) HO-1 was induced in astrocytes and Aβ(1-42) toxicity was significantly reduced, an effect which was reversed by the specific HO-1 inhibitor, QC-15. Our data suggest that Aβ(1-42) is toxic to astrocytes, but that induction of HO-1 affords protection against this toxicity due to formation of CO. HO-1 induction, or CO donors, would appear to present attractive possible approaches to provide protection of both neuronal and non-neuronal cell types from the degenerative effects of AD in the central nervous system

METEOROLOGICAL CONDITIONS DURING RECORD WILDFIRES IN THE PARANÁ RIVER DELTA: ANOMALIES AND APPLICATION OF A CLUSTERING MODEL

About 95 % of wildfires are caused by human activities. The burning of grasslands as a method of sweeping for livestock and agricultural exploitation has been implemented for over two centuries on the American continent. Every winter, fires are used to promote the regrowth of forage species in the Paraná River Delta. Unusual weather conditions and climate change have intensified the global impact of wildfires. In 2020, the accumulation and spread of unprecedented wildfire emissions affected the inhabitants of the Rosario Metropolitan Area (AMR), Argentina. This work analyzed meteorological conditions, the number of active fires detected by the VIIRS satellite instrument, and the concentration of fine particulate matter (PM2.5) measured in the AMR. Anomalies of precipitation, relative humidity, and temperature recorded in situ between June and August in the period 2010- 2020 were calculated. The results show that for the year 2020, ambient humidity and temperature had an average decrease of 10 % and 3 %, respectively, while accumulated precipitation had a reduction of about 70 % with respect to previous years.The clustering model showed that the highest median of Number of active fires (NI) coincides with the lowest accumulated precipitation and low relative humidity, as well as prevailing winds from the northwest. Wind analysis reveals that currents from the northwest direction promoted larger surface fire impacts in the Paraná River Delta, and northeast winds increased PM2.5 levels in the AMR. These findings underline the importance of considering meteorological conditions in assessing environmental risks and in formulating mitigation strategies against air pollution and forest fires

Bezlotoxumab for Prevention of Recurrent Clostridium difficile Infection

BACKGROUND Clostridium difficile is the most common cause of infectious diarrhea in hospitalized patients. Recurrences are common after antibiotic therapy. Actoxumab and bezlotoxumab are human monoclonal antibodies against C. difficile toxins A and B, respectively. METHODS We conducted two double-blind, randomized, placebo-controlled, phase 3 trials, MODIFY I and MODIFY II, involving 2655 adults receiving oral standard-of-care antibiotics for primary or recurrent C. difficile infection. Participants received an infusion of bezlotoxumab (10 mg per kilogram of body weight), actoxumab plus bezlotoxumab (10 mg per kilogram each), or placebo; actoxumab alone (10 mg per kilogram) was given in MODIFY I but discontinued after a planned interim analysis. The primary end point was recurrent infection (new episode after initial clinical cure) within 12 weeks after infusion in the modified intention-to-treat population. RESULTS In both trials, the rate of recurrent C. difficile infection was significantly lower with bezlotoxumab alone than with placebo (MODIFY I: 17% [67 of 386] vs. 28% [109 of 395]; adjusted difference, −10.1 percentage points; 95% confidence interval [CI], −15.9 to −4.3; P<0.001; MODIFY II: 16% [62 of 395] vs. 26% [97 of 378]; adjusted difference, −9.9 percentage points; 95% CI, −15.5 to −4.3; P<0.001) and was significantly lower with actoxumab plus bezlotoxumab than with placebo (MODIFY I: 16% [61 of 383] vs. 28% [109 of 395]; adjusted difference, −11.6 percentage points; 95% CI, −17.4 to −5.9; P<0.001; MODIFY II: 15% [58 of 390] vs. 26% [97 of 378]; adjusted difference, −10.7 percentage points; 95% CI, −16.4 to −5.1; P<0.001). In prespecified subgroup analyses (combined data set), rates of recurrent infection were lower in both groups that received bezlotoxumab than in the placebo group in subpopulations at high risk for recurrent infection or for an adverse outcome. The rates of initial clinical cure were 80% with bezlotoxumab alone, 73% with actoxumab plus bezlotoxumab, and 80% with placebo; the rates of sustained cure (initial clinical cure without recurrent infection in 12 weeks) were 64%, 58%, and 54%, respectively. The rates of adverse events were similar among these groups; the most common events were diarrhea and nausea. CONCLUSIONS Among participants receiving antibiotic treatment for primary or recurrent C. difficile infection, bezlotoxumab was associated with a substantially lower rate of recurrent infection than placebo and had a safety profile similar to that of placebo. The addition of actoxumab did not improve efficacy. (Funded by Merck; MODIFY I and MODIFY II ClinicalTrials.gov numbers, NCT01241552 and NCT01513239.

Stress suppresses and learning induces plasticity in CA3 of rat hippocampus: a three-dimensional ultrastructural study of thorny excrescences and their postsynaptic densities

Chronic stress and spatial training have been proposed to affect hippocampal structure and function in opposite ways. Previous morphological studies that addressed structural changes after chronic restraint stress and spatial training were based on two-dimensional morphometry which does not allow a complete morphometric characterisation of synaptic features. Here, for the first time in such studies, we examined these issues by using three-dimensional (3-D) reconstructions of electron microscope images taken from thorny excrescences of hippocampal CA3 pyramidal cells. Ultrastructural alterations in postsynaptic densities (PSDs) of thorny excrescences receiving input from mossy fibre boutons were also determined, as were changes in numbers of multivesicular bodies (endosome-like structures) within thorny excrescences and dendrites. Quantitative 3-D data demonstrated retraction of thorny excrescences after chronic restraint stress which was reversed after water maze training, whilst water maze training alone increased thorny excrescence volume and number of thorns per thorny excrescence. PSD surface area was unaffected by restraint stress but water maze training increased both number and area of PSDs per thorny excrescence. In restrained rats that were water maze trained PSD volume and surface area increased significantly. The proportion of perforated PSDs almost doubled after water maze training and restraint stress. Numbers of endosome-like structures in thorny excrescences decreased after restraint stress and increased after water maze training. These findings demonstrate that circuits involving contacts between mossy fibre terminals and CA3 pyramidal cells at stratum lucidum level are affected conversely by water maze training and chronic stress, confirming the remarkable plasticity of CA3 dendrites. They provide a clear illustration of the structural modifications that occur after life experiences noted for their different impact on hippocampal function

Evaluación del impacto de la ingesta de arándano sobre los niveles de colesterol, glucosa y triglicéridos en ratas wistar alimentadas con dietas ricas en lípidos.

En México, una de las principales causas de muerte en personas de edad adulta son enfermedades coronarias. Según estudios realizados en los últimos años, el 26% de los mexicanos de la tercera edad presentan niveles altos de colesterol HDL (+200 mg/dl). Estos datos son muy similares a nivel mundial. Se estima que en México prevalecían índices elevados de desnutrición, aumentando las manifestaciones de mala nutrición por exceso (ENSANUT, 2012). El arándano o “blueberry” es un frutal menor perteneciente al género Vaccinium, de la familia Ericaceae (Sudzuki, 1983). El fruto del arándano es una baya casi esférica, que dependiendo de la especie y cultivar, su tamaño puede variar entre 0,7 a 1,5 cm de diámetro, con un color azul claro hasta oscuro, conteniendo en su interior hasta 100 semillas pequeñas (Buzeta, 1997). Numerosas investigaciones relacionan al arándano con el aumento de colesterol HDL, lo que estaría asociado a una disminución en la probabilidad de sufrir afecciones cardíacas; esto debido a su gran poder antioxidante. El objetivo de este trabajo es la medición de los efectos del consumo de arándano macerado sobre la reducción y control de los niveles de colesterol (LDL, HDL), glucosa y triglicéridos en ratas Wistar en edad reproductiva

Forest hydrology in Chile: Past, present, and future

This paper reviews the current knowledge of hydrological processes in Chilean temperate forests which extend along western South America from latitude 29° S to 56 ° S. This geographic region includes a diverse range of natural and planted forests and a broad sweep of vegetation, edaphic, topographic, geologic, and climatic settings which create a unique natural laboratory. Many local communities, endangered freshwater ecosystems, and downstream economic activities in Chile rely on water flows from forested catchments. This review aims to (i) provide a comprehensive overview of Chilean forest hydrology, to (ii) review prior research in forest hydrology in Chile, and to (iii) identify knowledge gaps and provide a vision for future research on forest hydrology in Chile. We reviewed the relation between native forests, commercial plantations, and other land uses on water yield and water quality from the plot to the catchment scale. Much of the global understanding of forests and their relationship with the water cycle is in line with the findings of the studies reviewed here. Streamflow from forested catchments increases after timber harvesting, native forests appear to use less water than plantations, and streams draining native forest yield less sediment than streams draining plantations or grassland/shrublands. We identified 20 key knowledge gaps such as forest groundwater systems, soil–plant-atmosphere interactions, native forest hydrology, and the effect of forest management and restoration on hydrology. Also, we found a paucity of research in the northern geographic areas and forest types (35-36 ° S); most forest hydrology studies in Chile (56 %) have been conducted in the southern area (Los Rios Region around 39-40 ° S). There is limited knowledge of the geology and soils in many forested areas and how surface and groundwater are affected by changes in land cover. There is an opportunity to advance our understanding using process-based investigations linking field studies and modeling. Through the establishment of a forest hydrology science “society” to coordinate efforts, regional and national-scale land use planning might be supported. Our review ends with a vision to advance a cross-scale collaborative effort to use new nation-wide catchment-scale networks Long-term Ecosystem Research (LTER) sites, to promote common and complementary techniques in these studies, and to conduct transdisciplinary research to advance sound and integrated planning of forest lands in Chile